Cancer of unknown primary site

This chapter covers cancer of unknown primary site (CUP), and includes information on epidemiology, molecular biology, pathology, and multidisciplinary management of clinicopathological subsets. Previously, these tumours were diagnosed and treated based on clinical presentation, light microscopy and clinical intuition. Today, the majority of cancers of unknown primary site are becoming less unknown, more accurately classified, and appropriately treated by the use of multiplex or genome-wide expression profiling platforms. These techniques allow for precise and correct knowledge of the true tumour origin, leading to more rational and effective treatment. However, there also may be genetic signatures that are primary-independent, pro-metastatic, and possibly CUP-specific.

Peritoneal mesothelioma

Malignant peritoneal mesothelioma (MPM) is a rare malignancy arising from the serosa of the abdominal cavity; its natural history is hallmarked by intra-abdominal disease progression. Peritoneal mesothelioma patients generally present with abdominal pain and/or ascites. Pathologically, a positive immunostain for calretinin has markedly increased the accuracy of diagnosis. A new staging system combining extent of tumour burden measured by the peritoneal cancer index (PCI), abdominal nodal status and extra-abdominal metastases has been demonstrated to reliably stratify patient outcomes after cytoreductive surgery (CRS) and hyperthermic perioperative chemotherapy (HIPEC). Over the past decade, the management of these patients has evolved as a multimodality treatment similar to ovarian cancer treatment and now involves CRS and HIPEC.

Rectal cancer and systemic therapy of colorectal cancer

In rectal cancer treatment, surgery is most important. Dissection outside the mesorectal fascia, total mesorectal excision is required for cure in most cases; a local procedure is possible in the earliest tumours. Appropriate staging is required prior to treatment decision to stratify patients into risk groups. In early tumours surgery alone is sufficient whereas in intermediate cancers local recurrence rates are too high and preoperative radiotherapy is indicated. A short-course schedule is convenient, low toxic, although some prefer long-course chemoradiotherapy. The addition of a fluoropyrimidine enhances the radiotherapy. In locally advanced tumours preoperative chemoradiotherapy is required. The value of adjuvant chemotherapy in rectal cancer is controversial, particularly if preoperative chemoradiotherapy was used. Palliative chemotherapy prolongs life and improves well-being in patients with metastatic disease. Targeted drugs further improves the results to some extent. In some patients, chemotherapy may convert non-readily resectable metastases to resectable, and result in long-term cure.

Gastric cancer

This chapter covers gastric cancers, beginning with epidemiology and molecular biology, including the association between Helicobacter pylori infection and gastric cancer, and other genetic and environmental causes. The role of surgical therapy in the treatment of gastric cancer including staging and resection with curative intent is presented. The medical management of gastric cancer is discussed, including adjuvant therapy after curative surgery and systemic treatment for palliation of metastatic disease, taking into account the differing biology and treatments in the East and West. The use of the first biologics in gastric cancer, trastuzumab and ramucirumab, and their mechanisms of action are described. Various modes of palliation of symptoms in patients with advanced gastric cancer include: gastrojejunostomy, endoscopic placement of a self-expandable metallic stent for gastric stenosis or obstruction, and pain control with pain medications and radiotherapy.

Cancer survivorship and rehabilitation

A cancer diagnosis is often a life-changing event. Cancer survivorship has become an integral part of cancer care. Currently, two-thirds of patients survive at least five years after their cancer diagnosis and the proportion is increasing. Key components of survivorship care include: (1) surveillance for recurrence and screening for second primary cancers; (2) identification and management of long-term and late effects of the cancer and cancer treatments (3) improving modifiable health behaviours; and (4) care coordination. Late effects can be physical or psychosocial. Development of clinical practice guidelines that incorporate evidence-based recommendations is critical, as is further research to understand the full impact of cancer on patients’ lives.

Familial cancer syndromes and genetic counselling

Thanks to the veritably logarithmic advances in the molecular genetics of many emerging hereditary cancer syndromes, genetic counselling has become of paramount importance. It is a key element of the emerging concepts for patient education and management, which have become the clinical bedrock for diagnosis and management of hereditary cancer. Genetic counsellors have become proficient in the understanding of the complexities of molecular genetics in relation to hereditary cancer syndromes, demonstrating their ability both to supplement and replace the customary physician’s role in this overall process. We have used colorectal cancer, in particular Lynch syndrome, as a clinical genetic model based on the authors’ experience with diagnosis, DNA testing, and counselling of thousands of families for over four decades. Undoubtedly, the surface of the proverbial iceberg has barely been grazed in regard to the developments for the genetic counseling discipline.

Cancer control planning

Despite all the progress made in cancer research and in the fight against cancer, the disease cannot be completely eradicated in the foreseeable future. A logical public health measure must therefore focus all efforts on preventing and confining the disease, i.e. a systematic and coordinated approach to reduce the impact of cancer on populations. Such an organised approach is called cancer control. It forms part of a holistic and coordinated approach, called a national cancer control plan/ programme (NCCP), involving the public sector, non-governmental organizations, academia, and the private sector. Policy makers and cancer advocacy groups should consider cancer control planning, and its financing and implementation, a public health necessity and not an option. The model proposed here is a hybrid one. The success of cancer control planning depends greatly on the availability and functionality of local cancer data and knowledge, in addition to adequate resources and government commitment.

Health economic assessment of cancer therapy

Our ability to deliver high-quality cancer care is increasingly influenced by our ability to understand and manage the costs of care. Though there are considerable differences in the ways healthcare is financed and administered in different nations, there is a common need to deliver high-quality care at sustainable costs. This chapter reviews recent estimates of the aggregate costs of cancer care, discusses methods for determining cost-effectiveness or value in cancer care, provides a framework for understanding the components of cost at the societal and individual levels, and discusses efforts to control cost while preserving or improving both quality and outcomes.

Practice points for surgical oncology

Cancer surgery remains the cornerstone of curative cancer treatment for most solid cancers. Staging, resectability and timing of surgery should be discussed in a multidisciplinary team. Complete resection offers the best prognosis at many stages. Anatomical planes of surgery need to be taught and respected to reduce locoregional recurrence rate. Age, comorbidities, and patient preferences are important to consider before surgical treatment is advised. Minimal invasive techniques have shown equivalence in oncologic outcome for certain cancer types and established benefits in short-term outcomes. A laparoscopic approach is even sometimes possible. It remains important to select patients for these techniques according to medical history, staging, and fitness. In specialized centres locally advanced disease can be treated by a multimodal approach. The quality of surgery can be improved using standardized audit structures to monitor and feed back on outcome of surgery such as resected margins, infectious complications, and disease-free and overall survival.

Aetiology and progression of cancer

Worldwide, there is a large difference in cancer rates. These rates may change over generations when people move from one part of the world to another. This occurs because these generations adapt their lifestyle to that of the host country, indicating that lifestyle factors are important in the aetiology of cancer. In this chapter an overview of established associations between body fatness, physical activity, diet, and other lifestyle factors and the development of cancer is given. About one-third of all cancers worldwide are caused by an unhealthy lifestyle. Evidence-based recommendations for the general population to decrease their risk of cancer have been set. Guidelines for individuals who are diagnosed with cancer, however, are lacking, due to limited evidence on the role of lifestyle during and after cancer treatment. Research should now be directed towards the role of body fatness, physical activity, diet, and other lifestyle factors in cancer progression.